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Abstract: A male neonate presented with severe weakness, hypotonia, contractures and congenital scoliosis. Skeletal muscle specimens showed marked atrophy and degeneration of fast fibers with striking nemaline rods and hypertrophy of slow fibers that were ultrastructurally normal. A neuromuscular gene panel identified a homozygous essential splice variant in TNNT3 (chr11:1956150G > A, NM_006757.3:c.681+1G > A). TNNT3 encodes skeletal troponin‐Tfast and is associated with autosomal dominant distal arthrogryposis. TNNT3 has not previously been associated with nemaline myopathy (NM), a rare congenital myopathy linked to defects in proteins associated with thin filament structure and regulation. cDNA studies confirmed pathogenic consequences of the splice variant, eliciting exon‐skipping and intron retention events leading to a frameshift. Western blot showed deficiency of troponin‐Tfast protein with secondary loss of troponin‐Ifast. We establish a homozygous splice variant in TNNT3 as the likely cause of severe congenital NM with distal arthrogryposis, characterized by specific involvement of Type‐2 fibers and deficiency of troponin‐Tfast. [ABSTRACT FROM AUTHOR]

1 Populations of subdioecious species contain female, male and cosexual plants. Here we investigate factors influencing gender expression and patterns of resource allocation among the sex phenotypes in subdioecious populations of the diminutive geophyte Wurmbea dioica (Colchicaceae) from the Australian Capital Territory, south-east Australia. 2 Demographic studies and population comparisons of the sex phenotypes were conducted to determine their distinguishing features, and whether sex expression was labile. Comparisons of biomass allocation were made to assess whether plants with hermaphrodite flowers were larger than unisexual plants. The seed fertilities of sex phenotypes were measured and related to the sex ratio of populations. 3 Female plants exhibited canalized gender producing only ovuliferous flowers, which were smaller and less showy compared to flowers of other plants. Some male plants displayed labile gender expression, producing varying numbers of male and hermaphrodite flowers (fruiting males). Maternal investment among male plants was size-dependent. 4 Fruiting males were significantly larger and produced more flowers than unisexual plants. At flowering, we found no evidence for changes in proportional allocation with increases in size after controlling for total biomass. At fruiting, allocation patterns differed between females and fruiting males independently of size. 5 Total seed output by fruiting males was 70% of that produced by females. The number of seeds per fruit declined acropetally in both sexes, and males produced, on average, more seeds per fruit than females. Data on the relation between female frequency and the relative seed fertilities of males and females gave a poor fit to Lloyd's (1976) genetic model predicting equilibrium female frequency. The lack of congruence probably occurs because size-dependent gender modification in males complicates the assumptions of the model. Keywords: allocation strategies, sex ratios, sexual dimorphism, size-dependent gender modification

Rett syndrome is a clinically defined neurodevelopmental disorder almost exclusively affecting females. Usually sporadic, Rett syndrome is caused by mutations in the X-linked MECP2 gene in ∼90-95% of classic cases and 40-60% of individuals with atypical Rett syndrome. Mutations in the CDKL5 gene have been associated with the early-onset seizure variant of Rett syndrome and mutations in FOXG1 have been associated with the congenital Rett syndrome variant. We report the clinical features and array CGH findings of three atypical Rett syndrome patients who had severe intellectual impairment, early-onset developmental delay, postnatal microcephaly and hypotonia. In addition, the females had a seizure disorder, agenesis of the corpus callosum and subtle dysmorphism. All three were found to have an interstitial deletion of 14q12. The deleted region in common included the PRKD1 gene but not the FOXG1 gene. Gene expression analysis suggested a decrease in FOXG1 levels in two of the patients. Screening of 32 atypical Rett syndrome patients did not identify any pathogenic mutations in the PRKD1 gene, although a previously reported frameshift mutation affecting FOXG1 (c.256dupC, p.Gln86ProfsX35) was identified in a patient with the congenital Rett syndrome variant. There is phenotypic overlap between congenital Rett syndrome variants with FOXG1 mutations and the clinical presentation of our three patients with this 14q12 microdeletion, not encompassing the FOXG1 gene. We propose that the primary defect in these patients is misregulation of the FOXG1 gene rather than a primary abnormality of PRKD1. [ABSTRACT FROM AUTHOR]